US8445715B2 - Method of synthesizing fenofibrate - Google Patents
Method of synthesizing fenofibrate Download PDFInfo
- Publication number
- US8445715B2 US8445715B2 US12/600,515 US60051508A US8445715B2 US 8445715 B2 US8445715 B2 US 8445715B2 US 60051508 A US60051508 A US 60051508A US 8445715 B2 US8445715 B2 US 8445715B2
- Authority
- US
- United States
- Prior art keywords
- fenofibric acid
- solvent
- fenofibrate
- isopropyl
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related, expires
Links
- 238000000034 method Methods 0.000 title claims abstract description 37
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 229960002297 fenofibrate Drugs 0.000 title claims abstract description 23
- 230000002194 synthesizing effect Effects 0.000 title 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 38
- MQOBSOSZFYZQOK-UHFFFAOYSA-N fenofibric acid Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1C(=O)C1=CC=C(Cl)C=C1 MQOBSOSZFYZQOK-UHFFFAOYSA-N 0.000 claims abstract description 32
- 229960000701 fenofibric acid Drugs 0.000 claims abstract description 29
- -1 isopropyl halide Chemical class 0.000 claims abstract description 26
- 239000002904 solvent Substances 0.000 claims abstract description 24
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 239000000203 mixture Substances 0.000 claims abstract description 13
- 229910052751 metal Inorganic materials 0.000 claims abstract description 12
- 239000002184 metal Substances 0.000 claims abstract description 12
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical group CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 claims description 13
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 7
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 5
- 229940011051 isopropyl acetate Drugs 0.000 claims description 5
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 159000000000 sodium salts Chemical class 0.000 claims description 2
- 159000000007 calcium salts Chemical class 0.000 claims 1
- 229910003002 lithium salt Inorganic materials 0.000 claims 1
- 159000000002 lithium salts Chemical class 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000000746 purification Methods 0.000 abstract description 3
- 238000001953 recrystallisation Methods 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 238000006243 chemical reaction Methods 0.000 description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 238000001914 filtration Methods 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 235000011181 potassium carbonates Nutrition 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 238000005886 esterification reaction Methods 0.000 description 4
- 150000007529 inorganic bases Chemical class 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- RUETVLNXAGWCDS-UHFFFAOYSA-N (4-chlorophenyl)-(4-hydroxyphenyl)methanone Chemical compound C1=CC(O)=CC=C1C(=O)C1=CC=C(Cl)C=C1 RUETVLNXAGWCDS-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- RKIDDEGICSMIJA-UHFFFAOYSA-N 4-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C=C1 RKIDDEGICSMIJA-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- MWUSAETYTBNPDG-UHFFFAOYSA-N (4-chlorobenzoyl) 4-chlorobenzoate Chemical compound C1=CC(Cl)=CC=C1C(=O)OC(=O)C1=CC=C(Cl)C=C1 MWUSAETYTBNPDG-UHFFFAOYSA-N 0.000 description 1
- BIDDLDNGQCUOJQ-KAMYIIQDSA-N (z)-2,3-diphenylprop-2-enoic acid Chemical compound C=1C=CC=CC=1/C(C(=O)O)=C/C1=CC=CC=C1 BIDDLDNGQCUOJQ-KAMYIIQDSA-N 0.000 description 1
- ILPUOPPYSQEBNJ-UHFFFAOYSA-N 2-methyl-2-phenoxypropanoic acid Chemical compound OC(=O)C(C)(C)OC1=CC=CC=C1 ILPUOPPYSQEBNJ-UHFFFAOYSA-N 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- PYELQUCLANWPHD-UHFFFAOYSA-N C.CC(C)(OC1=CC=C(C(=O)C2=CC=C(Cl)C=C2)C=C1)C(=O)O.CC(C)Br.CC(C)OC(=O)C(C)(C)OC1=CC=C(C(=O)C2=CC=C(Cl)C=C2)C=C1.I.II.I[IH]I Chemical compound C.CC(C)(OC1=CC=C(C(=O)C2=CC=C(Cl)C=C2)C=C1)C(=O)O.CC(C)Br.CC(C)OC(=O)C(C)(C)OC1=CC=C(C(=O)C2=CC=C(Cl)C=C2)C=C1.I.II.I[IH]I PYELQUCLANWPHD-UHFFFAOYSA-N 0.000 description 1
- YYLLIJHXUHJATK-UHFFFAOYSA-N Cyclohexyl acetate Chemical compound CC(=O)OC1CCCCC1 YYLLIJHXUHJATK-UHFFFAOYSA-N 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 150000001559 benzoic acids Chemical class 0.000 description 1
- AQNQQHJNRPDOQV-UHFFFAOYSA-N bromocyclohexane Chemical compound BrC1CCCCC1 AQNQQHJNRPDOQV-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229940125753 fibrate Drugs 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 238000010978 in-process monitoring Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000002608 ionic liquid Substances 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- PZQSQRCNMZGWFT-QXMHVHEDSA-N propan-2-yl (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC(C)C PZQSQRCNMZGWFT-QXMHVHEDSA-N 0.000 description 1
- UNZJYKKJZGIFCG-UHFFFAOYSA-N propan-2-yl 2-bromo-2-methylpropanoate Chemical compound CC(C)OC(=O)C(C)(C)Br UNZJYKKJZGIFCG-UHFFFAOYSA-N 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- WBQTXTBONIWRGK-UHFFFAOYSA-N sodium;propan-2-olate Chemical compound [Na+].CC(C)[O-] WBQTXTBONIWRGK-UHFFFAOYSA-N 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- PYVOHVLEZJMINC-UHFFFAOYSA-N trihexyl(tetradecyl)phosphanium Chemical compound CCCCCCCCCCCCCC[P+](CCCCCC)(CCCCCC)CCCCCC PYVOHVLEZJMINC-UHFFFAOYSA-N 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/10—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with ester groups or with a carbon-halogen bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/10—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with ester groups or with a carbon-halogen bond
- C07C67/11—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with ester groups or with a carbon-halogen bond being mineral ester groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/67—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids
- C07C69/708—Ethers
- C07C69/712—Ethers the hydroxy group of the ester being etherified with a hydroxy compound having the hydroxy group bound to a carbon atom of a six-membered aromatic ring
Definitions
- the invention relates to a novel process for the synthesis of fenofibrate.
- This compound is an isopropyl ester of fenofibric acid and various processes have been provided for its industrial manufacture.
- fenofibrate is preferably obtained with a good yield by reaction of 4-chloro-4′-hydroxybenzophenone with isopropyl 2-bromo-2-methylpropanoate in the absence of solvent and in the presence of an alkaline agent, such as, in particular, potassium carbonate (EP 0 245 156 B1).
- an alkaline agent such as, in particular, potassium carbonate
- WO 02/062743 discloses a process for the preparation of fibrates similar to the preceding process but in which the phenol is reacted with an alkyl 2-bromo-2-methylpropionate in the presence of potassium bicarbonate and in a solvent chosen from C 1 -C 4 ketones and alcohols.
- a solvent chosen from C 1 -C 4 ketones and alcohols chosen from C 1 -C 4 ketones and alcohols.
- the only example described in this document relates to fenofibrate and the solvent used is isopropanol.
- the reaction time is much greater than in the case of the solvent-free process.
- the document EP 0 002 151 discloses a different process according to which the methyl ester of 2-methyl-2-phenoxypropanoic acid is reacted with 4-chlorobenzoyl chloride or 4-chlorobenzoic anhydride in a halogenated solvent in the presence of a Lewis acid, such as boron trifluoride (Friedel-Crafts reaction).
- a Lewis acid such as boron trifluoride
- the latter method exhibits the advantage of using inexpensive reactants and thus of producing fenofibrate with an advantageous material cost.
- the industrial implementation of the esterification stage requires large amounts of sulfuric acid in order to obtain good reaction kinetics, which results in frequent processing difficulties.
- the process for the preparation of fenofibrate according to the invention is thus characterized in that it consists in reacting, in a solvent composed of a mixture of dimethyl sulfoxide and of a C 2 -C 4 alkyl acetate, a metal salt of fenofibric acid with an isopropyl halide.
- the present invention relates to a novel process for producing fenofibrate starting from fenofibric acid, in which the esterification reaction is carried out using an alkyl halide and is performed in a specifically chosen solvent, according to the following reaction scheme:
- a general embodiment of the invention consists in reacting fenofibric acid with an inorganic base in a solvent system composed of a mixture of dimethyl sulfoxide and of a C 2 -C 4 alkyl acetate, so as to obtain a metal salt of fenofibric acid, such as, for example, a potassium or sodium salt, and then this salt is reacted with an isopropyl halide, at a temperature close to the reflux temperature of the reaction mixture at atmospheric pressure, in order to obtain fenofibrate in solution in the mixture.
- a metal salt of fenofibric acid such as, for example, a potassium or sodium salt
- the novelty of the present invention lies in the choice of the solvent system used for carrying out the reaction represented by the preceding reaction scheme.
- dimethyl sulfoxide and of C 2 -C 4 alkyl acetate used in the context of the present invention can vary within wide limits.
- a mixture of DMSO and of alkyl acetate so that the ratio of the total weight of solvent to the weight of the fenofibric acid is comprised between 0.2 and 3 and more preferably comprised between 0.4 and 2.
- the isopropyl halide is preferably isopropyl bromide (also known as 2-bromopropane).
- the metal salt of fenofibric acid is generally prepared by reaction (preferably carried out in the reaction medium) between fenofibric acid and a base, preferably an inorganic base.
- fenofibric acid is salified with potassium carbonate and the potassium salt obtained is reacted with isopropyl bromide in the same reaction medium.
- a mixture composed of fenofibric acid and of the solvent system is first prepared, followed by addition of a stoichiometric amount of a basic inorganic component capable of forming a salt with fenofibric acid.
- a stoichiometric amount of a basic inorganic component capable of forming a salt with fenofibric acid Use is more particularly made of potassium carbonate in order to obtain the potassium salt of fenofibric acid.
- An amount of an isopropyl halide (preferably 2-bromopropane) slightly greater than stoichiometric is subsequently added to the reaction mixture and the resulting mixture is brought to gentle reflux for 2 to 8 hours.
- the insoluble inorganic salts are removed by filtration and the solvent of the reaction is also removed and replaced by the crystallization solvent of fenofibrate. After cooling, the crystallized fenofibrate is isolated by filtration on a filtering device and dried.
- This process can be adapted to an industrial reactor (stainless or enameled steel) which makes possible the production of batches of approximately 1000 kg with 4000 l reactors under reaction time and capacity conditions compatible with an excellent productive output.
- the process according to the invention allows direct access to a product in agreement with the quality standards of Pharmacopoeia without the need for purification by recrystallization.
- These various aspects are also highly advantageous from the viewpoint of the protection of the environment since the by-products of the reaction are limited in amount and for the most part can be recycled.
- the entire process uses a very small amount of water and does not produce any wastes in the form of saline aqueous solutions.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0756220A FR2918366B1 (fr) | 2007-07-02 | 2007-07-02 | Nouveau procede de preparation du fenofibrate |
| FR0756220 | 2007-07-02 | ||
| PCT/EP2008/058511 WO2009004029A1 (fr) | 2007-07-02 | 2008-07-02 | Nouveau procede de synthese du fenofibrate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| US20120065421A1 US20120065421A1 (en) | 2012-03-15 |
| US8445715B2 true US8445715B2 (en) | 2013-05-21 |
Family
ID=39047765
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US12/600,515 Expired - Fee Related US8445715B2 (en) | 2007-07-02 | 2008-07-02 | Method of synthesizing fenofibrate |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US8445715B2 (it) |
| EP (1) | EP2170801B1 (it) |
| JP (1) | JP5442603B2 (it) |
| KR (1) | KR20100036231A (it) |
| CA (1) | CA2690869A1 (it) |
| EA (1) | EA016448B1 (it) |
| FR (1) | FR2918366B1 (it) |
| WO (1) | WO2009004029A1 (it) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11427528B2 (en) | 2016-07-29 | 2022-08-30 | Hangzhou Solipharma Co., Ltd. | Fenofibrate crystalline form and manufacturing method thereof |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103373921B (zh) * | 2012-04-26 | 2016-08-10 | 浙江海正药业股份有限公司 | 4-((取代苯基)二氟甲基)苯氧基羧酸衍生物及其制备方法和医药用途 |
| CN104276950B (zh) * | 2014-09-19 | 2016-04-20 | 徐州工业职业技术学院 | 一种智能控温、远程监控制备非诺贝特的方法 |
| CN108821973B (zh) * | 2018-08-14 | 2021-04-06 | 徐州工业职业技术学院 | 一种清洁生产普鲁脂芬的方法 |
| KR102829625B1 (ko) * | 2022-03-29 | 2025-07-04 | 한국바이오켐제약 주식회사 | 페노피브릭산의 정제방법 및 이에 의해 제조된 페노피브레이트 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4072705A (en) | 1975-02-12 | 1978-02-07 | Orchimed S.A. | Phenylmethylphenoxy propionic acid esters |
| EP0126361A1 (de) | 1983-05-20 | 1984-11-28 | Bayer Ag | Optisch aktive Propionsäure-Derivate |
| US20040073058A1 (en) | 2001-02-02 | 2004-04-15 | Giuseppe Guazzi | Process for the preparation of fibrates |
| US20040132995A1 (en) * | 2002-05-03 | 2004-07-08 | Orchid Chemicals & Pharmaceuticals, Ltd. | Process for the preparation of cephalosporins |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59225143A (ja) * | 1983-06-06 | 1984-12-18 | Kaken Pharmaceut Co Ltd | ビフエニリルプロピオン酸誘導体およびその製造法 |
| JPS63104939A (ja) * | 1986-10-20 | 1988-05-10 | Kiyuushin Seiyaku Kk | 新規カプロン酸誘導体 |
| JPH03188044A (ja) * | 1989-12-18 | 1991-08-16 | Tousoo Yuki Kagaku Kk | アシルオキシ脂肪族炭化水素の製造方法 |
| JPH072736A (ja) * | 1993-06-16 | 1995-01-06 | Dainippon Ink & Chem Inc | 二塩基酸エステルの製造方法 |
| JP5260826B2 (ja) * | 2005-12-12 | 2013-08-14 | 東ソー株式会社 | 高純度含フッ素（メタ）アクリル酸エステルの製造方法 |
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2007
- 2007-07-02 FR FR0756220A patent/FR2918366B1/fr not_active Expired - Fee Related
-
2008
- 2008-07-02 CA CA2690869A patent/CA2690869A1/fr not_active Abandoned
- 2008-07-02 JP JP2010513977A patent/JP5442603B2/ja not_active Expired - Fee Related
- 2008-07-02 EA EA201070078A patent/EA016448B1/ru not_active IP Right Cessation
- 2008-07-02 WO PCT/EP2008/058511 patent/WO2009004029A1/fr not_active Ceased
- 2008-07-02 KR KR1020097024345A patent/KR20100036231A/ko not_active Withdrawn
- 2008-07-02 US US12/600,515 patent/US8445715B2/en not_active Expired - Fee Related
- 2008-07-02 EP EP08774645.9A patent/EP2170801B1/fr active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4072705A (en) | 1975-02-12 | 1978-02-07 | Orchimed S.A. | Phenylmethylphenoxy propionic acid esters |
| EP0126361A1 (de) | 1983-05-20 | 1984-11-28 | Bayer Ag | Optisch aktive Propionsäure-Derivate |
| US20040073058A1 (en) | 2001-02-02 | 2004-04-15 | Giuseppe Guazzi | Process for the preparation of fibrates |
| US20040132995A1 (en) * | 2002-05-03 | 2004-07-08 | Orchid Chemicals & Pharmaceuticals, Ltd. | Process for the preparation of cephalosporins |
Non-Patent Citations (4)
| Title |
|---|
| Boros et al "Preparation of New 2,3-diphenylpropenoic Acid Esters-Good Yields Even for the More Hindered Z Isomers", Molecules, vol. 9, 2004, pp. 256-263. |
| http://en.wikipedia.org/wiki/Protic-solvent (Apr. 2012). * |
| http://www.chemicalland21.com/industrialchem/solalc/ISOPROPYL%20ACETATE.htm (Apr. 2012). * |
| Treu et al. (J. Heterocyclic Chem., 2002, 39, 1283). * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11427528B2 (en) | 2016-07-29 | 2022-08-30 | Hangzhou Solipharma Co., Ltd. | Fenofibrate crystalline form and manufacturing method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2010531852A (ja) | 2010-09-30 |
| EP2170801A1 (fr) | 2010-04-07 |
| KR20100036231A (ko) | 2010-04-07 |
| CA2690869A1 (fr) | 2009-01-08 |
| EA201070078A1 (ru) | 2010-06-30 |
| FR2918366A1 (fr) | 2009-01-09 |
| JP5442603B2 (ja) | 2014-03-12 |
| EP2170801B1 (fr) | 2014-03-26 |
| US20120065421A1 (en) | 2012-03-15 |
| EA016448B1 (ru) | 2012-05-30 |
| WO2009004029A1 (fr) | 2009-01-08 |
| FR2918366B1 (fr) | 2009-10-23 |
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